Toripalimab Combined With Gemcitabine/5--fluoropyrimidine for Advanced Cholangiocarcinoma

NCT03982680 | Unknown Phase 2 DMC

• 1 other identifier: cholangiocarcinoma
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a phase II clinical trial of single arm. The purpose is to evaluate the safety and efficacy of anti-PD-1 antibody Toripalimab combined with chemotherapy(gemcitabine+5-fluorine pyrimidine) in unresectable advanced cholangiocarcinoma patients.

Conditions

Advanced Cholangiocarcinoma

Outcome Measures

Primary Outcomes (3)

• 6-month PFS rate

  the rate of 6-month progression free survival

  6-month after the beginning of first line systemic therapy

• mPFS

  the median of progression free survival

  from the beginning of the first line systemic therapy until the date of first documented progression or date of death from any cause,whichever came first,assessed up to 24 months

• Toxic side effects

  assess according to the National Cancer Institute-Common Terminology Criteria for Adverse Events 3.0

  from the beginning of the first line systemic therapy until the end of follow-up,assessed up to 24 months

Secondary Outcomes (4)

• ORR

  from the beginning of the first line systemic therapy until the date of completion of therapy,assessed up to 13 months

• DCR

  from the beginning of the first line systemic therapy until the date of completion of therapy,assessed up to 13 months

• 1-year OS rate

  1 year after the beginning of the first line systemic therapy

• mOS

  from the beginning of the first line systemic therapy until the date of death from any cause,assessed up to 24 months

Other Outcomes (2)

• the value of PD-1/PD-L1

  from the beginning of the first line systemic therapy until the end of follow-up,assessed up to 24 months

• the value of MMR

  from the beginning of the first line systemic therapy until the end of follow-up,assessed up to 24 months

Study Arms (1)

Toripalimab combined with Gem/5-FU

EXPERIMENTAL

All patients were given Toripalimab 3 mg/kg (day 1 and 15); Gem+5-FU (Gem 1250mg/m2+CF 200 mg/m2+5-FU400 mg/m2 intravenous drip+5-FU 2.4-3.6 g/m2 continuous intravenous drip for 48 hours), the first and fifteenth days, four weeks for a cycle, a total of four cycles.After 4 cycles, Toripalimab was maintained at 3 mg/kg Q3 w for a total of 1 year if the disease was not progressing or toxic side effects were tolerated.

Drug: Toripalimab; Drug: Gemcitabine; Drug: 5- fluorine pyrimidine

Interventions

Toripalimab DRUG

3mg/kg on d1 and d15 q4W\*4cycles，then 3mg/kg q3w for 1 year in total

Toripalimab combined with Gem/5-FU

Gemcitabine DRUG

1250mg/m2 on d1 and d15 q4W\*4cycles

Also known as: Gem

Toripalimab combined with Gem/5-FU

5- fluorine pyrimidine DRUG

400mg/m2 intravenous injection plus 5-FU 2.4g-3.6g/m2 continuous intravenous drip for 48h on d1 and d15 q4W\*4cycles

Also known as: 5-FU

Toripalimab combined with Gem/5-FU

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• histologically or cytologically confirmed cholangiocarcinoma
• stage IV disease,no system therapy for advanced disease
• one or more lesions that can be measured by imaging assessment
• to 70 years of age and life expectancy exceeds 3 months
• adequate specimens for detection of PD-1/PD-L1 and MMR
• karnofsky performance status(KPS) score ≥70%
• routine blood routine, liver and kidney function and electrocardiogram were basically normal without contraindication of chemotherapy.

You may not qualify if:

• dual cancers other than cholangiocarcinoma
• metastasis of central nervous system
• unreleased biliary obstruction
• acute infections requiring treatment
• non-infectious pneumonia requires glucocorticoid therapy, active autoimmune diseases, or systemic immunosuppressive therapy.

Sponsors & Collaborators

• Jiangmen Central Hospital: lead

Study Sites (1)

Jiangmen central hospital

Jiangmen, Guangdong, 529000, China

RECRUITING

Related Publications (12)

• GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015 Jan 10;385(9963):117-71. doi: 10.1016/S0140-6736(14)61682-2. Epub 2014 Dec 18.

  PMID: 25530442 BACKGROUND

• Jain A, Javle M. Molecular profiling of biliary tract cancer: a target rich disease. J Gastrointest Oncol. 2016 Oct;7(5):797-803. doi: 10.21037/jgo.2016.09.01.

  PMID: 27747093 BACKGROUND

• Takakura H, Domae S, Ono T, Sasaki A. The Immunological Impact of Chemotherapy on the Tumor Microenvironment of Oral Squamous Cell Carcinoma. Acta Med Okayama. 2017 Jun;71(3):219-226. doi: 10.18926/AMO/55204.

  PMID: 28655941 BACKGROUND

• Gotwals P, Cameron S, Cipolletta D, Cremasco V, Crystal A, Hewes B, Mueller B, Quaratino S, Sabatos-Peyton C, Petruzzelli L, Engelman JA, Dranoff G. Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat Rev Cancer. 2017 May;17(5):286-301. doi: 10.1038/nrc.2017.17. Epub 2017 Mar 24.

  PMID: 28338065 BACKGROUND

• Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S, Funakoshi A, Nagino M, Kondo S, Nagaoka S, Funai J, Koshiji M, Nambu Y, Furuse J, Miyazaki M, Nimura Y. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 2010 Aug 10;103(4):469-74. doi: 10.1038/sj.bjc.6605779. Epub 2010 Jul 13.

  PMID: 20628385 BACKGROUND

• Morizane C, Ueno M, Ikeda M, Okusaka T, Ishii H, Furuse J. New developments in systemic therapy for advanced biliary tract cancer. Jpn J Clin Oncol. 2018 Aug 1;48(8):703-711. doi: 10.1093/jjco/hyy082.

  PMID: 29893894 BACKGROUND

• Sabbatino F, Villani V, Yearley JH, Deshpande V, Cai L, Konstantinidis IT, Moon C, Nota S, Wang Y, Al-Sukaini A, Zhu AX, Goyal L, Ting DT, Bardeesy N, Hong TS, Fernandez-del Castillo C, Tanabe KK, Lillemoe KD, Ferrone S, Ferrone CR. PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma. Clin Cancer Res. 2016 Jan 15;22(2):470-8. doi: 10.1158/1078-0432.CCR-15-0715. Epub 2015 Sep 15.

  PMID: 26373575 BACKGROUND

• Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, Chen L, Pardoll DM, Topalian SL, Anders RA. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014 Oct 1;20(19):5064-74. doi: 10.1158/1078-0432.CCR-13-3271. Epub 2014 Apr 8.

  PMID: 24714771 BACKGROUND

• Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014 Nov 27;515(7528):563-7. doi: 10.1038/nature14011.

  PMID: 25428504 BACKGROUND

• Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.

  PMID: 22658127 BACKGROUND

• Gou M, Zhang Y, Si H, Dai G. Efficacy and safety of nivolumab for metastatic biliary tract cancer. Onco Targets Ther. 2019 Jan 25;12:861-867. doi: 10.2147/OTT.S195537. eCollection 2019.

  PMID: 30774373 BACKGROUND

• Asaoka Y, Ijichi H, Koike K. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015 Nov 12;373(20):1979. doi: 10.1056/NEJMc1510353. No abstract available.

  PMID: 26559583 BACKGROUND

MeSH Terms

Interventions

toripalimab; Gemcitabine; Fluorouracil

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Uracil; Pyrimidinones

Study Officials

• Yu gengsheng, master

  jiangmen cenctral hospital

  STUDY DIRECTOR

Central Study Contacts

Deng wenjing, master

CONTACT

(+86)07503165905; wjdeng2011@163.com

Yu gengsheng, master

CONTACT

(+86)07503165915; gengsheng_yu@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice director of Oncology department

Model Details: All patients were given Toripalimab 3 mg/kg (day 1 and 15); Gem+5-FU (Gem 1250mg/m2+CF 200 mg/m2+5-FU400 mg/m2 intravenous drip+5-FU 2.4-3.6 g/m2 continuous intravenous drip for 48 hours), the first and fifteenth days, four weeks for a cycle, a total of four cycles. After 4 cycles, Toripalimab was maintained at 3 mg/kg Q3 w for a total of 1 year if the disease was not progressing or toxic side effects were tolerated.

Study Record Dates

• First Submitted: June 7, 2019
• First Posted: June 11, 2019
• Study Start: July 13, 2019
• Primary Completion: May 30, 2021
• Study Completion: December 30, 2021
• Last Updated: July 16, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)